title: Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era.
abstract: BACKGROUND
  Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy.
  
  
  METHODS
  From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone.
  
  
  RESULTS
  We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08).
  
  
  CONCLUSIONS
  Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.
authors.affiliation: Divisione di Oncologia Medica, Istituto per la Ricerca e la Cura del Cancro, Candiolo, Torino, Italy. fmontemurro@ircc.mauriziano.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
authors.forename: Stefania
authors.initials: S
authors.lastname: Redana
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.forename: Michela
authors.initials: M
authors.lastname: Donadio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valabrega
authors.forename: Barbara
authors.initials: B
authors.lastname: del Curto
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: dei Tos
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Jacomuzzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
authors.forename: Saverio
authors.initials: S
authors.lastname: Danese
authors.forename: Matteo
authors.initials: M
authors.lastname: Clavarezza
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
authors.forename: Silvana
authors.initials: S
authors.lastname: Di Palma
authors.forename: Antonio
authors.initials: A
authors.lastname: Durando
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human